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Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea pig entero-endocrine system: cellular distributions and intercellular heterogeneities

Summary

The family of the chromogranin/secretogranin proteins consists of three major subtypes: chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). These proteins are present in various endocrine cells and organs. Using immunohistochemistry on serial semithin sections, we have investigated ten endocrine cell types of the guinea pig gastro-intestinal tract for their content of chromogranin/secretogranin proteins. The gastrin cell was the only cell type containing immunoreactivities for all three chromogranin subtypes. The majority of entero-endocrine cells showed immunoreactivities for CgA and SgII. Somatostatin cells lacked immunoreactivities for any of the chromogranins. Moreover, the densities of the corresponding immunoreactivities varied among the different endocrine cell types or even among endocrine cells of a given population. Aminergic endocrine cells (e.g., enterochromaffin and enterochromaffin-like cells) regularly exhibited strong immunoreactivities for CgA but failed to react for SgII. In peptidergic endocrine cells, the immunoreactivities for both CgA and SgII ranged from dense to faint. This was also true for CgB in gastrin cells. Hence, only CgA and SgII can be considered as regular constituents of entero-endocrine cells. The intercellular differences in immunoreactivities for all three chromogranin subtypes indicate that every endocrine cell has its own composition of chromogranin/secretogranin proteins. This may be due to differences in the regulation of biosynthesis or processing of the chromogranins in individual endocrine cells; this in turn might be related to the functional states of endocrine cells.

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References

  • Bargsten G, Grube D, Forssmann WG, Winkler H (1988) Chromogranins and serotonin metabolism in entero-endocrine cells. Acta Endocrinol [Suppl] 287:29–30

    Google Scholar 

  • Benedum UM, Lamouroux A, Konecki DS, Rosa P, Hille A, Baeuerle PA, Frank R, Lottspeich F, Mallet J, Huttner WB (1987) The primary structure of human secretogranin I (chromogranin B): comparison with CgA reveals homologous terminal domains and a large intervening variable region EMBO J 6:1203–1211

    Google Scholar 

  • Benjannet S, Leduc R, Adrouche N, Falgueyret JP, Marcinkiewicz M, Seidah NG, Mbikay M, Lazarre C, Chretien M (1987) Chromogranin B (secretogranin I) a putative precursor of two novel peptides through processing at paired basic residues. FEBS Lett 224:142–148

    Google Scholar 

  • Buffa R, Marè P, Gini A, Salvadore M (1988) Chromogranins A and B and secretogranin II in hormonally identified endocrine cells of the gut and pancreas. Basic Appl Histochem 32:471–484

    Google Scholar 

  • Cetin Y (1990a) Secretin-cells of the mammalian intestine contain serotonin. Histochemistry 93:601–606

    Google Scholar 

  • Cetin Y (1990b) A novel endocrine cell type in the guinea-pig gastric mucosa: cellular source of proenkephalin-derived peptides. A histochemical, immunohistochemical, and electron microscopical characterization. Histochemistry 94:31–44

    Google Scholar 

  • Cetin Y, Grube D (1990) Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea-pig endocrine pancreas. Histochemistry 94:479–484

    Google Scholar 

  • Cetin Y, Müller-Köppel L, Aunis D, Bader M-F, Grube D (1989) Chromogranin A (CgA) in the gastro-entero-pancreatic (GEP) endocrine system. II. CgA in mammalian entero-endocrine cells. Histochemistry 92:265–275

    Google Scholar 

  • Ehrhart M, Grube D, Bader MF, Aunis D, Gratzl M (1986) Chromogranin A in the pancreatic islet: cellular and subcellular distribution. J Histochem Cytochem 34:1673–1682

    Google Scholar 

  • Ehrhart M, Jörns A, Grube D, Gratzl M (1988) Cellular distribution and amount of chromogranin A in bovine endocrine pancreas. J Histochem Cytochem 36:467–472

    Google Scholar 

  • Eiden LE (1987) Is chromogranin a prohormone? Nature 325:301

    Google Scholar 

  • Eiden LE, Huttner WB, Mallet J, O'Connor DT, Winkler H, Zanini A (1987) A nomenclature proposal for the chromogranin/secretogranin proteins. Neuroscience 21:1019–1021

    Google Scholar 

  • Facer P, Bishop AE, Lloyd RV, Wilson BS, Hennessy RJ, Polak JM (1985) Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract. Gastroenterology 89:1366–1373

    Google Scholar 

  • Falck B, Hillarp N-Å, Thieme G, Torp A (1962) Fluorescence of catecholamines and related compounds condensed with formaldehyde. J Histochem Cytochem 10:348–354

    Google Scholar 

  • Fischer-Colbrie R, Frischenschlager I (1985) Immunological characterization of secretory proteins of chromaffin granules: chromogranins A, chromogranins B and enkephalin-containing peptides. J Neurochem 44:1854–1861

    Google Scholar 

  • Fischer-Colbrie R, Lassmann H, Hagn C, Winkler H (1985) Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissue. Neuroscience 16:547–555

    Google Scholar 

  • Fischer-Colbrie R, Hagn C, Kilpatrick L, Winkler H (1986) Chromogranin C: a third component of the acidic proteins in chromaffin granules. J Neurochem 47:318–321

    Google Scholar 

  • Fischer-Colbrie R, Hagn C, Schober M (1987) Chromogranins A, B and C: widespread constituents of secretory vesicles. Ann NY Acad Sci 493:121–134

    Google Scholar 

  • Fischer-Colbrie R, Iacangelo A, Eiden LE (1988) Neural and humoral factors separately regulate neuropeptide Y, enkephalin, and chromogranin A and B mRNA levels in rat adrenal medulla. Proc Natl Acad Sci USA 85:3240–3244

    Google Scholar 

  • Forss-Petter S, Danielson P, Battenberg E, Bloom F, Sutcliffe JG (1989) Nucleotide sequence and cellular distribution of rat chromogranin B (secretogranin I) mRNA in neuroendocrine system. J Mol Neurosci 1:63–75

    Google Scholar 

  • Funakoshi A, Miyasaka K, Nakamura R, Kitani K, Funakoshi S, Tamamura H, Fujii N, Yajima H (1988) Bioactivity of synthetic human pancreastatin on exocrine pancreas. Biochem Biophys Res Commun 156:1237–1242

    Google Scholar 

  • Gazdar AF, Helman LJ, Israel MA, Russell EK, Linnoila RI, Mulshine JL, Schuller HM, Park J-G (1988) Expression of neuroendocrine cell markers L-DOPA decarboxylase, chromogranin A, and dense core granules in human tumors of endocrine and nonendocrine origin. Cancer Res 48:4078–4082

    Google Scholar 

  • Gerdes H-H, Phillips E, Huttner WB (1988) The primary structure of rat secretogranin II deduced from a cDNA sequence. Nucleic Acids Res 16:11811–11812

    Google Scholar 

  • Gerdes H-H, Rosa P, Phillips E, Baeuerle PA, Frank R, Argos P, Huttner WB (1989) The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH- and calcium-induced aggregation. J Biol Chem 264:12009–12015

    Google Scholar 

  • Gorr S-U, Shioi J, Cohn DV (1989) Interaction of calcium with porcine adrenal chromogranin A (secretory protein-I) and chromogranin B (secretogranin I). Am J Physiol 257:247–254

    Google Scholar 

  • Grube D (1986) The endocrine cells of the digestive system: amines, peptides, and modes of action. Anat Embryol 175:151–162

    Google Scholar 

  • Grube D, Aunis A, Bader F, Cetin Y, Jörns A, Yoshie S (1986) Chromogranin A (CGA) in the gastro-entero-pancreatic (GEP) endocrine system. I. CGA in the mammalian endocrine pancreas. Histochemistry 85:441–452

    Google Scholar 

  • Grube D, Bargsten G, Cetin Y, Yoshie S (1989) Chromogranins in mammalian GEP endocrine cells: their distribution and interrelations with co-stored amines and peptides. Arch Histol Cytol [Suppl] 52:91–98

    Google Scholar 

  • Hagn C, Schmid KW, Fischer-Colbrie R, Winkler H (1986) Chromogranin A, B, and C in human adrenal medulla and endocrine tissues. Lab Invest 55:405–411

    Google Scholar 

  • Huttner WB, Benedum UM (1987) Chromogranin A and pancreastatin. Nature 325:305

    Google Scholar 

  • Hutton JC, Davidson HW, Peshavaria M (1987) Proteolytic processing of chromogranin A in purified insulin granules. Biochem J 244:457–464

    Google Scholar 

  • Hutton JC, Peshavaria M, Johnston CF, Ravazzola M, Orci L (1988) Immunolocalization of betagrinin: a chromogranin A-related protein of the pancreatic B-cell. Endocrinology 122:1014–1020

    Google Scholar 

  • Iacangelo A, Fischer-Colbrie R, Koller KJ, Brownstein MJ, Eiden LE (1988) The sequence of porcine chromogranin A messenger RNA demonstrates chromogranin A can serve as the precursor for the biologically active hormone, pancreastatin. Endocrinology 122:2339–2341

    Google Scholar 

  • Konecki DS, Benedum UM, Gerdes HH, Huttner WB (1987) The primary structure of human chromogranin A and pancreastatin. J Biol Chem 262:17026–17030

    Google Scholar 

  • Lewis JJ, Zdon MJ, Adrian TE, Modlin IM (1988) Pancreastatin: a novel peptide inhibitor of parietal cell secretion. Surgery 104:1031–1036

    Google Scholar 

  • Lloyd RV, Cano M, Rosa P, Hille A, Huttner WB (1988) Distribution of chromogranin A and secretogranin I (chromogranin B) in neuroendocrine cells and tumors. Am J Pathol 130:296–304

    Google Scholar 

  • Lloyd RV, Iacangelo A, Eiden LE, Cano M, Jin L, Grimes M (1989) Chromogranin A and B messenger ribonucleic acids in pituitary and other normal and neoplastic human endocrine tissues. Lab Invest 60:548–556

    Google Scholar 

  • O'Connor DT, Mezger M, Chang YM (1987) Catecholamines interact with chromogranins (Cgs), the major catecholamine storage vesicle (CSV) soluble core proteins. Kidney Int 31:305

    Google Scholar 

  • Pagani A, Papotti M, Höfler H, Weiler R, Winkler H, Bussolati G (1990) Chromogranin A and B gene expression in carcinomas of the breast. Correlation of immunocytochemical, immunoblot, and hybridization analyses. Am J Pathol 136:319–327

    Google Scholar 

  • Pearse AGE (1969) The cytochemistry and ultrastructure of poly-peptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem 17:303–313

    Google Scholar 

  • Pearse AGE, Polak JM, Adams C, Kendall PA (1974) Diethylpyrocarbonate, a varpour-phase fixative for immunofluorescence studies on polypeptide hormones. Histochem J 6:347–352

    Google Scholar 

  • Rieker S, Fischer-Colbrie R, Eiden L, Winkler H (1988) Phylogenetic distribution of peptides related to chromogranins A and B. J Neurochem 50:1066–1073

    Google Scholar 

  • Rindi G, Buffa R, Sessa F, Tortora O, Solcia E (1986) Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Histochemistry 85:19–28

    Google Scholar 

  • Rosa P, Hille A, Lee RHW, Zanini A, De Camilli P, Huttner WB (1985) Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol 101:1999–2011

    Google Scholar 

  • Rundle S, Somogyi P, Fischer-Colbrie R, Hagn C, Winkler H, Chubb IW (1986) Chromogranin A, B and C: immunohistochemical localization in ovine pituitary and the relationship with hormone-containing cells. Regul Pept 16:217–233

    Google Scholar 

  • Siegel RE, Iacangelo A, Park J, Eiden LE (1988) Chromogranin A biosynthetic cell populations in bovine endocrine and neuronal tissues: detection by in situ hybridization histochemistry. Mol Endocrinol 2:368–374

    Google Scholar 

  • Sietzen M, Schober M, Fischer-Colbrie R, Scherman D, Sperk G, Winkler H (1987) Rat adrenal medulla: levels of chromogranins, enkephalins, dopamine beta-hydroxylase and of the amine transporter are changed by nervous activity and hypophysectomy. Neuroscience 22:131–139

    Google Scholar 

  • Simon J-P, Aunis D (1989) Biochemistry of the chromogranin A protein family. Biochem J 262:1–13

    Google Scholar 

  • Simon J-P, Bader M-F, Aunis D (1989) Effect of secretagogues on chromogranin A synthesis in bovine cultured chromaffin cells. Possible regulation by protein kinase C. Biochem J 260:915–922

    Google Scholar 

  • Sternberger LA (1986) Immunohistochemistry, 3rd edn. Wiley, New York

    Google Scholar 

  • Tatemoto K, Efendic S, Mutt V, Makk G, Feistner GJ, Barchas JD (1986) Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324:476–478

    Google Scholar 

  • Waschek JA, Pruss RM, Siegel RE, Eiden LE, Bader MF, Aunis D (1987) Regulation of enkephalin, VIP, and chromogranin biosynthesis in actively secreting chromaffin cells — multiple strategies for multiple peptides. Ann NY Acad Sci 493:308–323

    Google Scholar 

  • Weiler R, Feichtinger H, Schmid KW, Fischer-Colbrie R, Grimelius L, Cedermark B, Papotti M, Bussolati G, Winkler H (1987) Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids. Virchows Arch [A] 412:103–109

    Google Scholar 

  • Weiler R, Fischer-Colbrie R, Schmid KW, Feichtinger H, Bussolati G, Grimelius L, Krisch K, Kerl H, O'Connor D, Winkler H (1988) Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors. Am J Surg Pathol 12:877–884

    Google Scholar 

  • Westermann R, Stögbauer F, Unsicker K, Lietzke R (1988) Calcium-dependence of chromogranin A-catecholamine interaction. FEBS Lett 239:203–206

    Google Scholar 

  • Wiedenmann B, Huttner WB (1989) Synaptophysin and chromogranins/secretogranins — widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Arch [B] 58:95–121

    Google Scholar 

  • Wiedenmann B, Waldherr R, Buhr H, Hille A, Rosa P, Huttner WB (1988) Identification of gastroenteropancreatic neuroendocrine cells in normal and neoplastic human tissue with antibodies against synaptophysin, chromogranin A, secretogranin I (chromogranin B), and secretogranin II. Gastroenterology 95:1364–1374

    Google Scholar 

  • Winkler H, Apps DK, Fischer-Colbrie R (1986) The molecular function of adrenal chromaffin granules: established facts and unresolved topics. Neuroscience 18:261–290

    Google Scholar 

  • Wohlfarter T, Fischer-Colbrie R, Hogue-Angeletti R, Eiden LE, Winkler H (1988) Processing of chromogranin A within chromaffin granules starts at C- and N-terminal cleavage sites. FEBS Lett 231:67–70

    Google Scholar 

  • Yoshie S, Hagn C, Ehrhart M, Fischer-Colbrie R, Grube D, Winkler H, Gratzl M (1987) Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet. Histochemistry 87:99–106

    Google Scholar 

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Cetin, Y., Grube, D. Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea pig entero-endocrine system: cellular distributions and intercellular heterogeneities. Cell Tissue Res 264, 231–241 (1991). https://doi.org/10.1007/BF00313960

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Key words

  • Chromogranin
  • Secretogranin
  • Enteroendocrine cells
  • Immunohistochemistry
  • Guinea pig